Purpose: Myeloid suppressor (Gr-1 + /CD11b + ) cells accumulate in the spleens of tumor-bearing mice where they contribute to immunosuppression by inhibiting the function of CD8 + Tcells and by promoting tumor angiogenesis. Elimination of these myeloid suppressor cells may thus significantly improve antitumor responses and enhance effects of cancer immunotherapy, although to date few practical options exist. Experimental Design: The effect of the chemotherapy drug gemcitabine on the number of (Gr-1 + /CD11b + ) cells in the spleens of animals bearing large tumors derived from five cancer lines grown in both C57Bl/6 and BALB/c mice was analyzed. Suppressive activity of splenocytes from gemcitabine-treated and control animals was measured in natural killer (NK) cell lysis and Winn assays. The impact of myeloid suppressor cell activity was determined in an immunogene therapy model using an adenovirus expressing IFN-h. Results:This study shows that the chemotherapeutic drug gemcitabine, given at a dose similar to the equivalent dose used in patients, was able to dramatically and specifically reduce the number of myeloid suppressor cells found in the spleens of animals bearing large tumors with no significant reductions in CD4 + T cells, CD8 + T cells, NK cells, macrophages, or B cells. The loss of myeloid suppressor cells was accompanied by an increase in the antitumor activity of CD8 + T cells and activated NK cells. Combining gemcitabine with cytokine immunogene therapy using IFN-h markedly enhanced antitumor efficacy. Conclusions: These results suggest that gemcitabine may be a practical strategy for the reduction of myeloid suppressor cells and should be evaluated in conjunction with a variety of immunotherapy approaches.

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We designed and synthesized new alkyl-functionalized organic dyes, MK-1 and MK-2, for dye-sensitized solar cells (DSSCs). Based on the MK-2 dye, a high performance of efficiency (eta, 7.7%; short-circuit current density Jsc = 14.0 mA cm-2, open-circuit voltage Voc = 0.74 V, and fill factor FF = 0.74) was achieved under AM 1.5 G irradiation (100 mW cm-2). Remarkably, the relatively higher Voc for DSSCs based on MK-1 and MK-2 dyes, which have long alkyl chains, were observed among the organic dyes caused by the increasing of the electron lifetime in the conduction band of TiO2. Our molecular design of alkyl-functionalized dyes strongly suggests the promising performance of molecular photovoltaics based on organic dyes.

Background: Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies. Methods: Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level. Results: Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; PϽ.001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant asso

IRE1 plays an essential role in the endoplasmic reticulum (ER) stress response in yeast and mammals. We found that a double mutant of Arabidopsis IRE1A and IRE1B (ire1a/ire1b) is more sensitive to the ER stress inducer tunicamycin than the wild-type. Transcriptome analysis revealed that genes whose induction was reduced in ire1a/ire1b largely overlapped those in the bzip60 mutant. We observed that the active form of bZIP60 protein detected in the wild-type was missing in ire1a/ire1b. We further demonstrated that bZIP60 mRNA is spliced by ER stress, removing 23 ribonucleotides and therefore causing a frameshift that replaces the C-terminal region of bZIP60 including the transmembrane domain (TMD) with a shorter region without a TMD. This splicing was detected in ire1a and ire1b single mutants, but not in the ire1a/ire1b double mutant. We conclude that IRE1A and IRE1B catalyse unconventional splicing of bZIP60 mRNA to produce the active transcription factor.

Destruction of cancer cells by therapeutic antibodies occurs, at least in part, through antibody-dependent cellular cytotoxicity (ADCC), and this can be mediated by various Fc-receptor-expressing immune cells, including neutrophils. However, the mechanism(s) by which neutrophils kill antibody-opsonized cancer cells has not been established. Here, we demonstrate that neutrophils can exert a mode of destruction of cancer cells, which involves antibody-mediated trogocytosis by neutrophils. Intimately associated with this is an active mechanical disruption of the cancer cell plasma membrane, leading to a lytic (i.e., necrotic) type of cancer cell death. Furthermore, this mode of destruction of antibody-opsonized cancer cells by neutrophils is potentiated by CD47-SIRPα checkpoint blockade. Collectively, these findings show that neutrophil ADCC toward cancer cells occurs by a mechanism of cytotoxicity called trogoptosis, which can be further improved by targeting CD47-SIRPα interactions.

Electron diffusion coefficient, lifetime, and density in the TiO(2) electrode of dye-sensitized TiO(2) solar cells (DSCs) employing I(-)/I(3)(-) redox couples were measured with eight different metal-free organic dyes and three Ru complex dyes. At matched electron density, all DSCs using organic dyes (ODSCs) showed shorter electron lifetime with comparable or larger diffusion coefficients in comparison to the DSCs using the Ru dyes (RuDSC). The shorter lifetime was attributed partially to the slower dye cation reduction rate of the organic dyes by I(-), faster electron diffusion coefficient in the TiO(2), and mostly higher I(3)(-) concentration in the vicinity of the TiO(2) surface. Whereas a slight shift of the conduction band edge potential (E(cb)) of the TiO(2) was seen with a few organic dyes, no correlation was found with the dipole moment of the adsorbed dyes. This implies that the adsorbed dyes interact with cations in the electrolyte, so the direction of the dipole is altered or simply screened. The increase of [I(3)(-)] in the vicinity of the TiO(2) surface was interpreted with partial charge distribution of the dyes. Under one-sun conditions, less electron density due to shorter electron lifetime was found to be the main reason for the lower values of V(oc) for all ODSCs in comparison to that of RuDSCs. Among the organic dyes, having larger molecular size and alkyl chains showed longer electron lifetime, and thus higher V(oc). Toward higher open circuit voltage, a design guide of organic dyes controlling the electron lifetime is discussed.

We fabricated dye-adsorbed NiO solar cells (pDSCs) with six different metal-free organic dyes having various ground-state oxidation potentials. Under monochromatic light irradiation, all dyes showed cathodic current at wavelengths where the dyes absorb, suggesting hole injection occurred from the adsorbed dyes to the valence band of NiO. Absorbed photon-to-current conversion efficiency (APCE) tends to increase with the increase of energy difference (∆E) between the valence band edge of NiO and the ground state of the dyes. The maximum APCE of 30% was obtained with 0.6 eV of the ∆E. The apparent hole diffusion coefficient in the NiO electrode was nearly independent from light intensity, and the values were estimated to be 4 × 10 -8 cm 2 /s. On the other hand, hole lifetime depends on light intensity, ranging from 3 × 10 -2 to 1 × 10 0 s. Investigation of the anchoring site of the dyes and the results of molecular orbital calculations suggested that electron injection from the dye to the valence band of NiO, occurring just after the hole injection, is the major factor of the relatively low efficiency even with the case of large ∆E.